Hydrophobic CDR3 residues promote the development of self-reactive T cells

Studies of individual T cells receptors (TCRs) have shed some light on structural features that underlie self-reactivity. However, general rules that predict whether TCRs are self-reactive have not been fully elucidated. Analyses of thymocytes expressing all V(β) family members show that the interfacial hydrophobicity of amino acids at positions 6 and 7 of the CDR3β segment robustly promotes the development of self-reactive TCRs. An index based on these findings distinguishes V(β)2(+), V(β)6(+) and V(β)8.2(+) regulatory T cells from conventional T cells, as well as T cells selected on a major histocompatibility complex (MHC) allele associated with mouse type-1 diabetes from those selected on a non-autoimmune promoting MHC. These results provide a means for distinguishing normal and autoimmune-prone T cell repertoires.